Astrocyte heterogeneity is closely associated with the pathophysiology of traumatic brain injury (TBI), particularly in the development of cerebral edema, which is a major contributor to morbidity and mortality in patients with TBI. However, little is known about how certain astrocyte subpopulations contribute to the development of cerebral edema after acute brain injury. Using multiomics approaches, we identified a proinflammatory interferon regulatory factor-1–positive (IRF1 ⁺ ) astrocyte cluster that correlates with clinical severity and outcomes in patients with TBI. Mechanistically, IRF1 in astrocytes binds to promoters of inflammatory cytokine genes, driving neurotoxicity and disrupting endothelial tight junction integrity. Using Aldh1l1 ^CreERT2 ; Irf1 ^flox/flox mice, we demonstrated that astrocyte-specific deletion of Irf1 mitigates astrocyte-mediated pathogenic activities, ameliorates blood-brain barrier (BBB) disruption, and reduces cerebral edema after TBI. Moreover, enhanced IRF1 activity in astrocytes facilitates the recruitment of CD8 ⁺ T cells by releasing C-X-C motif chemokine ligand 10 (CXCL10), which exacerbates BBB disruption and cerebral edema. Furthermore, we identified tet methylcytosine dioxygenase 3 (TET3)–mediated DNA hydroxymethylation as a key epigenetic mechanism that up-regulates IRF1 expression in astrocytes, thereby activating proinflammatory transcriptional programs. Finally, we developed an IRF1 antagonist, 8003-3282, which effectively reduces inflammation, preserves BBB integrity, alleviates cerebral edema, and improves neurological outcomes in a TBI mouse model. These findings highlight IRF1 ⁺ astrocytes as critical mediators of TBI-associated pathology and suggest that targeting this astrocyte cluster may represent a promising therapeutic strategy to mitigate inflammation, BBB damage, and cerebral edema in TBI.

OBJECTIVE: The authors aimed to explore the clinical outcomes and risk factors related to recurrence of and survival from solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) that were reclassified according to the 2021 WHO classification of central nervous system (CNS) tumors. METHODS: The authors retrospectively collected and analyzed the clinical and pathological data of SFTs and HPCs recorded from January 2007 to December 2021. Two neuropathologists reassessed pathological slides and regraded specimens on the basis of the 2021 WHO classification. The prognostic factors related to progression-free survival (PFS) and overall survival (OS) were statistically assessed with univariate and multivariate Cox regression analyses. RESULTS: A total of 146 patients (74 men and 72 women, mean ± SD [range] age 46.1 ± 14.3 [3–78] years) were reviewed, and 86, 35, and 25 patients were reclassified as having grade 1, 2, and 3 SFTs on the basis of the 2021 WHO classification, respectively. The median PFS and OS of the patients with WHO grade 1 SFT were 105 months and 199 months after initial diagnosis; for patients with WHO grade 2 SFT, 77 months and 145 months; and for patients with WHO grade 3 SFT, 44 months and 112 months, respectively. Of the entire cohort, 61 patients experienced local recurrence and 31 died, of whom 27 (87.1%) died of SFT and relevant complications. Ten patients had extracranial metastasis. In multivariate Cox regression analysis, subtotal resection (STR) (HR 4.648, 95% CI 2.601–8.304, p < 0.001), tumor located in the parasagittal or parafalx region (HR 2.105, 95% CI 1.099–4.033, p = 0.025), tumor in the vertebrae (HR 3.352, 95% CI 1.228–9.148, p = 0.018), WHO grade 2 SFT (HR 2.579, 95% CI 1.343–4.953, p = 0.004), and WHO grade 3 SFT (HR 5.814, 95% CI 2.887–11.712, p < 0.001) were significantly associated with shortened PFS, whereas STR (HR 3.217, 95% CI 1.435–7.210, p = 0.005) and WHO grade 3 SFT (HR 3.433, 95% CI 1.324–8.901, p = 0.011) were significantly associated with shortened OS. In univariate analyses, patients who received adjuvant radiotherapy (RT) after STR had longer PFS than patients who did not receive RT. CONCLUSIONS: The 2021 WHO classification of CNS tumors better predicted malignancy with different pathological grades, and in particular WHO grade 3 SFT had worse prognosis. Gross-total resection (GTR) can significantly prolong PFS and OS and should serve as the most important treatment method. Adjuvant RT was helpful for patients who underwent STR but not for patients who underwent GTR.

Objectives: Rat models of global cerebral ischemia (GCI) are essential to study potential treatment strategies against stroke in humans. However, nonvisual electrocoagulation of vertebral arteries often leads to incomplete occlusion that may prevent the creation of a successful model. Methods: Therefore, we used a modified method in which the vertebral arteries were safely visualized and electrocauterized between the first and second transverse processes through a dorsal incision. Twenty-four hours later, GCI was induced by transient bilateral common carotid arterial occlusion using microvascular clips. The clips were removed after 10, 20, or 30 min of four-vessel occlusion. Results: Digital subtraction angiography demonstrated complete occlusion of the rat vertebral arteries. In the 20-min GCI group, the rats were monitored for 1, 3, 5, or 7 days followed by histological analysis. The results showed that neuronal death in the CA1 subregion occurred almost linearly between 1 and 3 days of recovery. Tape removal test was used for up to 7 days after 20 min of GCI or sham operation. The latency time was found to be significantly increased 1 to 7 days after GCI compared with sham. Conclusions: In conclusion, this modified model provides a reliable tool for ischemic stroke research.